The main goals of the present research are to develop new chemical approaches to the study of biological membranes, their detailed chemical organization, dynamics and structure-function relationships. One central problem is to understand the nature of specific interactions between phospholipids and membrane proteins and those between different phospholipids. New cross-linking approaches are being developed for these problems. Syntheses of a variety of fatty acids containing "built-in" photosensitive groups have been carried out. For in vivo studies, the synthetic fatty acid derivatives are being incorporated into fatty acid auxotrophs of E. coli, into a pseudomonad auxotroph (host for PM2 lipid shell virus) and into mammalian cells and their viruses, e.g., sindbis virus. Photolysis should yield information on the nearest neighbor interactions. In vitro studies of a variety of systems possessing membrane functions will be performed using defined membrane proteins and synthetic phospholipids prepared from the photosensitive fatty acids. In addition to information on protein-phospholipid interactions, insights into membrane biogenesis and topography should accrue from these studies. The systems being studied are: (1) lipopolysaccharide-phosphatidylethanolamine-glucosyl transferase interaction; (2) phosphoenolpyruvate dependent phosphotransferase system; (3) Ca ions pump of sarcoplasmic reticulum; (4) bacteriorhodopsin, a biological proton pump; (5) beta-hydroxybutyrate dehydrogenase-lecithin interactions; (6) the nature of phospholipid glycoprotein interactions in sindbis virus and PM2 virus. Membrane-DNA association will be investigated (a) by looking for a covalent linkage between DNA and a membrane component and by attempting crosslinks between any proteins that may be involved and replicating DNA. Some of the proteins involved in vivo DNA replication will thus be indentified.